The formation and maintenance of normal tissue architecture and morphological pattern are dependent on cell-cell recognition and adhesion and adhesive interactions with extracellular biomatrix, complex processes which today are only partly understood. This research will use immunological methods to identify macromolecules involved in cell-cell adhesion of normal and regenerating hepatocytes, or transplantable hepatocellular carcinomata induced in ACI rats by 2-acetylaminofluorene. Adhesion will be measured by the rate of aggregation in suspension or the rate of contact formation by cells attached to collagen substrata. Differential extraction techniques will be used to isolate components involved in the interaction of hepatocytes with extracellular biomatrix. Heteroantibodies and/or monoclonal antibodies will be raised against intact hepatocytes, biomatrix or isolated junctions. Reactivity of these antibodies with surface components involved in adhesion will be assessed by examining the ability of Fab fragments to inhibit aggregation or substrate adhesion. Biochemical and immunochemical techniques will be used in combination with antisera or antibodies demonstrating adhesion-blocking activity to isolate plasma membrane components involved in cell adhesion. Monoclonal antibodies will subsequently be raised against these putative cell adhesion molecules. Immunocytochemical techniques will be used to map the distribution of cell adhesion molecules during reaggregation of normal hepatocytes and transplantable tumor cells as well as in normal liver and primary and transplantable tumors. Immunochemical techniques will be used for comparative analysis of cell adhesion molecules immunoprecipated from NP-40 extracts of normal, regenerating and malignant hepatocytes. To date, we have raised two monoclonal antibodies against a 105,000 MW component which may be involved in the interaction of hepatocytes with biomatrix. In addition, we have produced monoclonal antibodies which recognize desmosomal junctions isolated from rat liver. We are currently investigating the ability of these Mabs to alter or inhibit reaggregation of normal hepatocytes. These studies should provide new information regarding the mechanism(s) of cellular adhesion and the role of this process in histotypic pattern formation of epithelial cells, thereby providing insight into cell-surface functions relevant to the expression of the malignant state.